Comparison of cytopathologic findings in patients with negative Pap test and positive high-risk HPV infection among three groups.

PURPOSE: Comparison of colposcopy-guided biopsy and endocervical cytologic (ECC) results in patients with negative Papanicolaou (Pap) and positive high-risk (HR) HPV tests in the three groups of HPV 16/18, non-16/18 HR-HPV (other HR-HPV), and concurrent infection of either HPV 16/18 and at least one subtype of other HR-HPVs. METHODS: This cross-sectional study was conducted among women aged 30-65 who had negative Pap and positive HR-HPV DNA tests. Pap test was performed using liquid cytology. For HPV DNA testing, the polymerase chain reaction (PCR) method was used. RESULTS: Among 394 participants, 111 (28.2%) were in the HPV 16/18, 226 (57.4%) in the Other HR-HPV, and 57 (14.4%) in the concurrent group. The mean age of participants was 35.71 ± 7.1 years. Cervical intraepithelial neoplasia (CIN) grade 2/3 were seen in 29 (26.1%) patients of HPV 16/18, 60 (26.5%) of other HR-HPV, and 18 (31.6%) of concurrent infection group (P = 0.593). HPV 52 was the most common subtype in the other HR-HPV group (15%). CONCLUSIONS: The risk of high-grade CIN lesions in patients with negative Pap test and positive other HR-HPV was not significantly less than patients with positive HPV 16/18. Besides, the risk of losing the patients to 1-year follow-up seems high.

Cell growth inhibition and apoptosis in breast cancer cells induced by anti-FZD7 scFvs: involvement of bioinformatics-based design of novel epitopes.

BACKGROUND: FZD7 has a critical role as a surface receptor of Wnt/ß-catenin signaling in cancer cells. Suppressing Wnt signaling through blocking FZD7 is shown to decrease cell viability, metastasis and invasion. Bioinformatic methods have been a powerful tool in epitope designing studies. Small size, high affinity and human origin of scFv antibodies have provided unique advantages for these recombinant antibodies. METHODS: Two epitopes from extracellular domain of FZD7 were designed using bioinformatic methods. Specific anti-FZD7 scFvs were selected against these epitopes through panning process. The specificity of the scFvs was assessed by phage ELISA and the ability to bind to FZD7 expressing cell line (MDA-MB-231) was determined by flowcytometry. Antiproliferative and apoptotic effects of the scFvs were evaluated by MTT and Annexin V/PI assays. The effects of selected scFvs on expression level of Surivin, c-Myc and Dvl genes were also evaluated by real-time PCR. RESULTS: Results demonstrated selection of two specific scFvs (scFv-I and scFv-II) with frequencies of 35 and 20%. Both antibodies bound to the corresponding peptides and cell surface receptors as shown by phage ELISA and flowcytometry, respectively. The scFvs inhibited cell growth of MDA-MB-231 cells significantly as compared to untreated cells. Growth inhibition of 58.6 and 53.1% were detected for scFv-I and scFv-II, respectively. No significant growth inhibition was detected for SKBR-3 negative control cells. The scFvs induced apoptotic effects in the MDA-MB-231 treated cells after 48 h, which were 81.6 and 74.9% for scFv-I and scFv-II, respectively. Downregulation of Surivin, c-Myc and Dvl genes were also shown after 48h treatment of cells with either of scFvs (59.3-93.8%). ScFv-I showed significant higher antiproliferative and apoptotic effects than scFv-II. CONCLUSIONS: Bioinformatic methods could effectively select potential epitopes of FZD7 protein and suggest that epitope designing by bioinformatic methods could contribute to the selection of key antigens for cancer immunotherapy. The selected scFvs, especially scFv-I, with high antiproliferative and apoptotic effects could be considered as effective agents for immunotherapy of cancers expressing FZD7 receptor including triple negative breast cancer.

Insilico analysis of three different tag polypeptides with dual roles in scFv antibodies.

Single chain fragment variable (scFv) antibodies are composed of variable heavy (VH) and variable light (VL) domains that are joined by a polypeptide linker. Typically, [(Gly4Ser) n] sequence is used as a linker to retain the integrity of the antigen-binding domain. Due to its low immunogenicity, this sequence cannot be used as a tag for scFv detection and purification. Several evidences have shown that the addition of an N or C-terminal tag for scFv detection and purification will result in the decreased expression and binding capacity of this antibody fragment. In this study, we substituted the traditional linker (GGGGS) with His-tag, C-myc or E-tag sequences through molecular modeling. Stability and integrity of all models were assessed by molecular dynamic (MD) simulation. Based on MD simulation analysis, the model containing E-tag sequence as a linker indicated more stability compared to other molecules. The results suggest that E-tag not only can be substituted for the traditional linker, also eliminates the necessity of using additional tag for scFv detection and purification.

Association of Interleukin-17A rs2275913 Polymorphism with Recurrent Miscarriage: A Systematic Review and Meta-Analysis Study.

Recurrent miscarriage (RM) is a condition defined as having three or more consecutive pregnancy losses before the 20 weeks of pregnancy. The present study was undertaken to investigate association of Interleukin-17A (IL-17A) rs2275913 polymorphism with RM. To this end, we searched the international databases (Web of Science, PubMed, Embase, and Scopus) and extracted studies investigating the association of IL-17A rs2275913 polymorphism with RM using the appropriate keywords. The collected data were analyzed with the random-effects model and STATA (version 14). A total of five studies met the eligibility criteria, and total sample size was 998 subjects. Mean age of the cases and controls were 31.41 ± 4.16 and 30.56 ± 3.5 years, respectively. Our results disclosed a significant relationship of the IL-17A rs2275913 AA genotype [odds ratio (OR)=1.68; 95% confidence interval (CI)=1.16- 2.43; I2=19; P=0.294) with RM. There was no statistically significant correlation between IL-17Ars2275913 GG genotype (OR=1.04; 95% CI=0.64-1.7; I2=59.5; P=0.042) and GA genotype (OR=0.85; 95% CI=0.65-1.12; I2=19.1; P=0.293) with RM. Our findings revealed that the IL-17A rs2275913 polymorphism is associated with RM, and the AA genotype of this polymorphism increased possibility of being involved in RM.

A highly potential cleavable linker for tumor targeting antibody-chemokines.

Chemokines are the large family of chemotactic cytokines that play an important role in leukocyte movement and migration stimulation. Until now, several antibody-cytokine (chemokine) fusion proteins have been investigated in clinical trials because of their ability to evoke the circulating leukocytes far from the tumor site. In this case, creating the concentration gradient regarding the chemokine is very important to recruit the circulating leukocytes with maximum performance to the tumor environment. To achieve a proper gradient, the chemokine separation from the tumor antigen-bounded antibody can be very crucial. Thus, we designed a novel linker that can be cleaved by enzymes presented around the tumor site including cathepsin B, urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). Also, it can inhibit tumor progression by competing with the native substrate of key proteases in the tumor microenvironment. The proposed linker was evaluated using some bioinformatics approaches. In silico results showed that the linker is structurally stable and could be detected and cleaved using the mentioned enzymes.Communicated by Ramaswamy H. Sarma.

Successful management of a patient with ovarian ectopic pregnancy by the end of the first trimester: a case report.

BACKGROUND: Among all ectopic pregnancies, between 0.5% and 3.5% are ovarian ectopic pregnancies, a potentially life-threatening condition when ruptured due to its serious potential for hemorrhaging. A majority of ovarian ectopic pregnancies are diagnosed by the 7th week of pregnancy when the patient becomes symptomatic, and ultrasound can be used to diagnose this condition. CASE PRESENTATION: We present the case of a 39-year-old Persian woman in the 12th week of gestation who presented with vaginal bleeding and abdominal pain and was diagnosed with ovarian ectopic pregnancy. Her notable laboratory finding was ß-human chorionic gonadotropin > 15,000, which indicates definite pregnancy. Transvaginal ultrasound (TVS) revealed no evidence of intrauterine pregnancy, but a well-circumscribed gestational sac in the left ovary. The patient was successfully treated with resection of the gestational sac and partial left salpingo-oophorectomy. Histopathological studies confirmed the diagnosis of ovarian ectopic pregnancy. CONCLUSION: The case emphasizes the ability of ovarian ectopic pregnancy to develop asymptomatically through the course of pregnancy and points to the necessity for high-quality prenatal care and the importance of determining the fetal site during pregnancy.

COVID-19 presenting as right flank pain in a postpartum woman: A case report.

INTRODUCTION: Patients with COVID-19 infection may present a wide range of symptoms that make its diagnosis challenging, especially in patients with underlying conditions. PRESENTATION OF CASE: A 30-year-old postpartum woman presented to the Emergency Department (ED) of Arash Women Hospital with right flank pain. Physical examination revealed tachycardia and decreased sounds in the base of the lung. Chest CT scan demonstrated patchy consolidations in bases of the lungs in favor of COVID-19 infection. The patient underwent pharmacotherapy with Remdesivir, steroid, and interferon beta-1a for eight days and was discharged in a good condition. DISCUSSION: This study suggests that involvement of lungs' bases may be associated with gastrointestinal symptoms such as abdominal or flank pain in the COVID-19 patients. It makes the diagnosis difficult in a scenario such as the described patient in our study where there may be other differential diagnoses correlating with the patient's clinical course. CONCLUSION: COVID-19 should be in the differential diagnosis of any patient presenting to ED with relevant complaints. Correct and immediate diagnosis is critical for proper treatment and isolation of patients with COVID-19.

Molecular systematics and distribution review of the endemic cyprinid species, Persian chub, Acanthobrama persidis (Coad, 1981) in Southern Iran (Teleostei: Cyprinidae).

The Iranian Persian chub is an endemic species of the family Cyprinidae known only from few localities in drainages of Southern Iran. It was originally described in the genus Pseudophoxinus as (Pseudophoxinus persidis) and then Petroleuciscus (as Petroleuciscus persidis). In this study, we examined phylogenetic relationships of the Iranian Persian chub with other relatives in the family Cyprinidae based on the mitochondrial cytochrome b gene to estimate the phylogenetic (and taxonomic) position of the species. Our molecular phylogenies show that new fish sequences from the drainages in southern Iran are clustered with sequences of the genus Acanthobrama from GenBank while the sequences from two other genera (Pseudophoxinus and Petroleuciscus) are in distinct clade. Therefore, we conclude that the populations of Persian Chub in drainages of southern Iran (i.e., Kol, Kor, Maharlu and Persis) belong to the genus Acanthobrama and species Acanthobrama persidis. The predicted geographic distributions for the species showed a large area of suitable climate for A. persidis across south and west of Iran especially in the Kor River basin. Some other parts in the Persis and Tigris are also might have been suitable habitats for this cyprinid species showing possible dispersal route of Acanthobrama from Tigris to the Persis, Kor and Kol basins.

Aphanius arakensis, a new species of tooth-carp (Actinopterygii, Cyprinodontidae) from the endorheic Namak Lake basin in Iran.

A new species of tooth-carp, Aphanius arakensissp. n., is described from the Namak Lake basin in Iran. The new species is distinguished by the congeners distributed in Iran by the following combination of characters: 10-12 anal fin rays, 28-32 lateral line scales, 10-13 caudal peduncle scales, 8-10 gill rakers, 12-19, commonly 15-16, clearly defined flank bars in males, a more prominent pigmentation along the flank added by relatively big blotches in the middle and posterior flank segments in females, a short but high antirostrum of the otolith that has a wide excisura, and a ventral rim with some small, drop-like processes, and 19 molecular apomorphies (17 transitions, two transversions) in the cytochrome b gene. It was suggested based on the phylogenetic analysis that the new species is sister to Aphanius sophiae from the Kor River and that Aphanius farsicus from the Maharlu Lake basin is sister to Aphanius arakensis plus Aphanius sophiae. A noticeable feature of the Aphanius diversity in Iran is the conservatism of the external morphology as well as morphometric and meristic characters, while distinctive differences are present in genetic characters, otolith morphology, and male color pattern. Transformation of the latter was probably driven by sexual selection.